Posters

Stroke is a leading cause of disability, with approximately 30% of ischaemic stroke survivors developing post-stroke pain (PSP). PSP is a chronic neuropathic pain condition, yet research into its underlying molecular and cellular mechanisms remains limited. Calcitonin gene-related peptide (CGRP) has been implicated in nociceptive signalling in neuropathic pain conditions; mitogen-activated protein kinases (MAPKs) in post-ischaemic inflammatory injury; and sustained glial activation in the maintenance of chronic pain states. Matrix metalloproteinase-9 (MMP9) has also been associated with post-stroke neuroinflammation and neuropathic pain. However, the contribution of these pain-related pathways to PSP has yet to be investigated.

This study aimed to characterise neuropathic pain mechanisms in a mouse model of PSP. Male and female C57BL/6 mice underwent permanent ischaemia induced by distal occlusion of the left middle cerebral artery (pMCAO). Dorsal root ganglia, spinal cord, and thalamic tissue were collected 28 days post-injury to assess changes in peripheral and central nociceptive pathways. Immunofluorescence analysis was performed using markers for CGRP, pERK, pP38, Iba1, GFAP, and MMP9. Imaging was conducted using a Leica DMi8 microscope and quantified using FIJI software.

Increased sensitivity in response to no painful mechanical stimulation was observed only contralateral to the site of injury. Similarly, expression of pain-related molecular markers was significantly increased in contralateral dorsal root ganglion, spinal cord, and thalamic tissue following pMCAO.

These findings highlight coordinated peripheral and central molecular changes underlying PSP and provide mechanistic insight into pathways that may represent future therapeutic targets for post-stroke neuropathic pain.

Introduction: Migraine is a highly disabling neurological disorder and a leading cause of years lived with disability worldwide. Despite its prevalence, disease-modifying treatments remain limited, reflecting an incomplete understanding of the mechanisms driving migraine progression and chronification. Clinical features such as cutaneous allodynia, reduced responsiveness to triptans, and sensitivity to nitric oxide donors implicate sustained trigeminovascular sensitisation in human migraine.

Objectives: Using a clinically relevant rodent model that reproduces key features of human migraine and medication overuse headache, we investigated whether migraine-like behaviours and trigger sensitivity are associated with peripheral and central sensitisation within the trigeminovascular system.

Methods: Rats received continuous subcutaneous infusion of sumatriptan or saline for six days to model medication overuse, a common contributor to chronic migraine in patients. Trigeminal ganglia (TG) and trigeminal nucleus caudalis (TNC) were collected either at day 6 or day 20 from infusion onset. To model clinically relevant migraine triggering, a subset of animals received sodium nitroprusside, a nitric oxide donor known to provoke migraine attacks in humans. Immunohistochemistry was used to assess markers of neuronal and glial activation (pERK, pp38, Iba-1, GFAP, NeuN). Results: Sumatriptan infusion induced sustained increases in activation markers in both TG and TNC, localised to nociceptive processing regions of the TNC. Notably, pERK and pp38 expression shifted from neuronal predominance at early time points to glial localisation at later stages, consistent with mechanisms implicated in migraine chronification in patients.

Conclusions: These findings identify progressive neuronal–glial sensitisation within the trigeminovascular system as a mechanistic substrate linking medication overuse, trigger sensitivity, and migraine chronification, supporting translational targets for disease-modifying therapies in human migraine.